BTA TRAK Assay and BTA Stat Test

BTA TRAK and BTA Stat tests (Bard Diagnostic Sciences Inc., Redmond, WA) are enzyme immunoassays intended for the measurement of human complement factor H related protein (hCFHrp) in urine using the two monoclonal antibodies X13.2 and X52.1.^21,22 Bladder tumour cells shed hCFHrp into urine, presumably to protect themselves from being destroyed by the complement system.²³ BTA TRAK is a quantitative assay, whereas BTA Stat is a quantitative test.

In various studies ^24–31 overall sensitivity of the BTA TRAK test was reported to be 64% (range 56% to 72%) and overall specificity to be 71% (51% to 95%) (see Table 2). The mean sensitivity for the BTA stat test (see Table 3) was 72% (range 57% to 100%) and the mean specificity was 74% (range 64% to 93%).^32–41 The diagnostic PPVs and NPVs of the BTA assays (see Table 7) ranged from 35% to 68% and 70% to 95%, respectively.^26,32,36,40 Sarosdy et al.⁴¹ evaluated the BTA stat test in the detection of recurrent bladder cancer and achieved 67% sensitivity (147/220). For those patients with previous cytologic results available, cytology had a sensitivity of 23% and the BTA stat test of 58% for detection of recurrent cancer (p<0.001). Ellis et al.³¹ found an overall sensitivity of 72% (151/216) with the BTA TRAK assay in patients with recurrent bladder cancer. In comparison with urine cytology BTA TRAK and BTA stat had higher sensitivities but lower specificities.^35,37,39,41 For low-grade and low-stage tumours the sensitivity is comparable with published sensitivities of urine cytology.33 The specificity of the BTA tests was found to be lower in patients with another genitourinary cancer or benign genitourinary disease such as haematuria, urinary tract inflammation, or renal calculi than in healthy volunteers.^36,37 Furthermore, intravesical bacillus Calmette-Guerin (BCG) treatment may result in up to 28% decreased specificity.³⁹ The BTA tests are superior to voided urine cytology in diagnosis of bladder cancer and detection of recurrent bladder cancer. Due to low specificity, BTA should not be used without first ruling out benign or malignant genitourinary disease, other than bladder cancer.

NMP22 and NMP22 BladderChek Test

NMP22 and NMP22 BladderChek (Matritech Inc., Newton, MA, US) are tests intended for the measurement of nuclear matrix protein 22, which is highly released into patients’ urine by apoptotic tumour cells. NMP22 is a quantitative immunoassay,while NMP22 BladderChek is a quantitative pointof- care test that can be performed in the office before or at the time of cystoscopy visit. Several studies ^35,40–51 have shown an overall sensitivity and specificity of 66% (range 47% to 89%) and of 75% (range 60% to 84%), respectively, for the NMP22 assay (see Table 4). There was an increase in sensitivity with increase in tumour stage and tumour grade.^43,49 Soloway et al.⁵¹ monitored disease status after endoscopic tumour resection and found 70% (23/33) of the recurrences. When urinary NMP22 and voided urine cytology were compared, NMP22 showed higher sensitivity in patients with urothelial cancer.^43,47,50 NMP22 is superior to cytology for detection of low-grade tumours, but with a limited specificity. Awareness and exclusion of benign lesions can increase the specificity, as Ponsky et al.⁴⁵ demonstrated. After exclusion of false-positive results in 608 patients, they found an overall sensitivity and specificity of 89% and 84%. NMP22 is approved by the FDA for screening for bladder cancer and it may be useful for diagnosing symptomatic patients or people with occupational exposure to known carcinogens like aromatic amines, polycyclic aromatic hydrocarbons, or chlorinated solvents. Only preliminary data on sensitivity and specificity (see Table 5) are available for NMP22 BladderChek.^52–55 Tomera et al.⁵⁵ identified 61% (11/18) transitional cell carcinoma including one ureteral carcinoma in high-risk patients. NMP22 BladderChek was more valuable than cytology with 18% sensitivity. Specificity of NMP22 BladderChek and cytology in patients determined not to have bladder cancer was 89% and 99%, respectively. Oehr ⁵³ excluded patients with urocystitis, stones, urinary tract infections (UTIs) and incorporated catheters and achieved a sensitivity and specificity of 82% and 98% in the haematuria group and of 61% and 98% in the followup group, respectively. Overall, for the NMP22 BladderChek test a lower rate of false-positive results was reported than for the NMP22 assay yielding higher PPVs and NPVs (see Table 7).^{40,42,44,45,47,48,51,53,54} The accuracy of NMP22 and NMP22 BladderChek, for the reliable diagnosis of patients at risk from bladder cancer has to be evaluated in a prospective multicentre study.